The small antifungal protein secreted by Penicillium chrysogenum (PAF) inhibits the growth of important zoo pathogenic filamentous fungi, including members of the Aspergillus family.It was shown previously that PAF has no toxic effects on mammalian cells in vitro. We carried out safety experiments by investigating the in vivo effects of PAF by inoculating adult C57/B16 mice with PAF intranasally. Animals were randomly divided into six groups and subjected to different PAF concentrations, up to 54 µg, either once a week for up to 8 weeks or once every day for two weeks. Animals neither died due to the treatment nor were any side effects observed. Histological examinations did not find any pathological reaction in the liver, in the mucous membrane of the nose, and in the lungs, even in the highest concentration used.Mass spectrometry revealed that ZZZ. The effect of the drug on the skin was examined in an irritative dermatitis model by measuring the thickness of the ears. This proved to be the same following PAF application as in control (23.8±9.2 vs. 22.5±5.0 µm, respectively) and significantly less than when treated with phorbol-12-myristate-13-acetate (PMA; 57.5±29.2 µm) used as positive control. Histological changes relative to control were present only in the case of PMA. Positron emission tomography was used to follow potential inflammation of the lungs. Neither the application of control saline nor that of PAF induced any inflammation while the positive control lipopolysaccharide did. Since no toxic effects of PAF were found either in intranasal application or in local external treatment, our result is the first step for introducing PAF as potential antifungal drug in human therapy.

PAF, a small antifungal protein from Penicillium chrysogenum, inhibits the growth of several pathogenic filamentous fungi, including members of the Aspergillus genus. PAF has been proven to have no toxic effects in vivo in mice by intranasal application. To test its efficacy against invasive pulmonary aspergillosis (IPA), experiments were carried out in mice suffering from IPA. Adult mice were immunosuppressed and then infected with Aspergillus fumigatus. After stable infection, the animals were inoculated with PAF intranasally at a concentration of 2.7 mg/kg twice per day. At this concentration—which is highly toxic in vitro to A. fumigatus—the mortality of the animals was slightly delayed but finally all animals died. Histological examinations revealed massive fungal infections in the lungs of both PAF-treated and untreated animal groups. Because intranasally administered PAF was unable to overcome IPA, modified and combined therapies were introduced. The intraperitoneal application of PAF in animals with IPA prolonged the survival of the animals only 1 day. Similar results were obtained with amphotericin B (AMB), with PAF and AMB being equally effective. Combined therapy with AMB and PAF—which are synergistic in vitro—was found to be more effective than either AMB or PAF treatment alone. As no toxic effects of PAF in mammals have been described thus far, and, moreover, there are so far no A. fumigatus strains with reported inherent or acquired PAF resistance, it is worth carrying out further studies to introduce PAF as a potential antifungal drug in human therapy.

Although statins, the most widely used drugs in the treatment of hyperlipidaemia, are generally accepted as efficient and safe drugs their side-effects on skeletal muscle have been reported with increasing frequency in the past years. The lack of an appropriate animal model in which these side effects would consistently be observed is one of the most important drawbacks in studying statin associated myopathy. To overcome this and enable the studying of the effects of fluvastatin on skeletal muscles an animal model with high blood cholesterol levels was developed. In these animals cholesterol levels rose more than seven fold (from soleus the duration of twitch and tetanic force was shortened. These results clearly indicate that statin administration in these animals results in a myopathy characterized by decreased muscle force and elevated plasma creatine kinase level.

Aspergillus fumigatus is an opportunistic pathogen, the leading cause of invasive and disseminated aspergillosis in systemic immunocompromised patients, and an important cause of mortality. The aim of the present study was to adapt a pulmonary aspergillosis murine model, to determine pathodynamical parameters quantitatively, and to follow the progression of fungal infection in vivo. The nasal inoculation of Aspergillus conidia in mice previously subjected to immunosuppression with cyclophosphamide (CP) turned out to be a more suitable model than that of immunosuppressed with hydrocortisone (HC). The following parameters were found to correlate quantitatively with the progress of the infection: (i) survival rate, (ii) weight loss of mice, (iii) infected focal plaque size, (iv) hyphal density, (v) hyphal length distribution of A. fumigatus, and the (vi) the histopathological status and scores. These parameters will be essential elements for the development of antifungal drugs and therapies, and important for the investigation of the pathogenicity in different strains of A. fumigatus.